Field of the Invention
The invention relates to modified soluble VEGF receptor-1 (also known as sFlt1) genes, nucleic acid vectors including the modified genes, optimized viral capsids including the modified genes, methods of using the modified genes in the treatment of diseases related to ocular neovascularization, such as macular degeneration.
Discussion of Related Art
Leading causes of severe vision loss and blindness are ocular-related disorders wherein the vasculature of the eye is damaged or insufficiently regulated. Ocular-related diseases comprising a neovascularization aspect are many and include, for example, exudative age-related macular degeneration, diabetic retinopathy, corneal neovascularization, choroidal neovascularization, neovascular glaucoma, cyclitis, Hippel-Lindau Disease, retinopathy of prematurity, pterygium, histoplasmosis, iris neovascularization, macular edema, glaucoma-associated neovascularization, and the like.
Damage of the retina, i.e., retinal detachment, retinal tears, or retinal degeneration, is directly connected to vision loss. A common cause of retinal detachment, retinal tears, and retinal degeneration is abnormal, that being, uncontrolled vascularization of various ocular tissues.
It has been found that vascular endothelial growth factor (VEGF) is a major stimulatory factor for retinal neovascularisation. It is unlikely to be the only stimulatory factor but it is nevertheless the key factor involved. VEGF is upregulated by hypoxia and its levels are increased in the retina and vitreous of patients or laboratory animals with ischaemic retinopathies. Also, increased expression of VEGF in retinal photoreceptors stimulates neovascularisation in the retina and VEGF antagonists inhibit retinal or iris neovascularisation in animal models.
For many ocular-related disorders, no efficient therapeutic options currently are available. Laser photocoagulation involves administering laser burns to various areas of the eye and is used in the treatment of many neovascularization-linked disorders. Laser treatment does not guarantee that vision loss will be attenuated. In fact, many patients afflicted with age-related macular degeneration eventually experience severe vision loss in spite of treatment. Other treatment options for ocular-related disorders include thermotherapy, radiation therapy, surgery, e.g., macular translocation, removal of excess ocular tissue, drug therapy, and the like. However, in most cases, all available treatment options have limited therapeutic effect, require repeated, costly procedures, and/or are associated with dangerous side-effects.
Given the prevalence of ocular-related disorders, there remains a need for an effective prophylactic and therapeutic treatment of ocular-related disorders. Accordingly, the invention provides materials and methods for achieving a beneficial effect in the eye, such as inhibiting or reducing angiogenesis or preventing photoreceptor cell loss. This and other advantages of the invention will become apparent from the detailed description provided herein.